Major histocompatibility genes (MHG) code for cell membrane components involved in immune response regulation. The objective of this proposal is to refine our basic understanding of the genetics of these components and their phenotypic and functional expression in respect to immune differentiation. Since it became increasingly clear that all species, including man, display a general similarity with respect to their histocompatibility antigen system, genetically-defined animal models are the most suited to investigate the genetic fine structure, gene action regulation and evolution of this system, specifically in respect to the peculiarities of cell differentiation leading to immunocompetence and its deviations. The major efforts of this proposal are: 1) to improve the possibility of investigating the genetic basis and functional aspects of these phenomena by continuation of production of specifically-needed congenic rat lines; 2) the search for and selection of recombinants regarding cell membrane antigens and functionally recognizable traits such as mixed lymphocyte culture reaction, immune responsiveness, and susceptibility to disease; and 3) to elucidate the serological, biological, and molecular properties of gene products regulating immune responsiveness in rats and mice. Fifteen congenic lines are now in production, three taken over from the colony of Dr. J. Palm are nearly completed (N12) and others are in the second to fifth backcross generation.